See the publication which contains this
article in full (reprinted by kind consent of the
Pacific Neuropsychiatric Institute)
Neppe, VM. Integration of the Evaluation
and Management of the Transient Closed Head Injury
Patient: Some Directions.
Chapter 19, Pages 421-450. In Varney, N. and
Roberts, R. (editors) Evaluation and Treatment
of Mild Traumatic Brain Injury.
Published by Erlbaum and Associates, Mahweh, NJ. 1999.

BACKGROUND TO ASSESSMENT OF THE CHIT

We have defined the "closed head injury
syndrome of transient kind" (CHIT) as having several
subtypes: a physiological brain injury of the post
concussional dimension (PCCHITs), a psychological
dysfunction of post-traumatic kind (PTCHITs), a focal
residual kind (FRCHITs) or combinations mixed with
these (MCHITs). Further, there is a synergistic physical,
cognitive and psychological synergism across the post
traumatic functional syndrome and legitimate brain
injury and predisposing factors and degrees of physiological
brain reserve may determine exact manifestations of
a CHIT. (Neppe and Goodwin, In Press)

We have seen how "minor" CHI is often
not minor. The misnomer of mild often is linked with
significant and brief, or no impairments of consciousness
may be associated with significant residua of the
CHIT. Some patients may manifest pathoplastic compensations
less with pre-existing conditions such that the symptoms
of the CHIT may relate to the straw that broke the
camel's back. Additionally, the actual pathogenetic
changes in CHITs may manifest in both focal and generalized
forms. (Neppe and Goodwin, In Press)

We have demonstrated how time based
evaluations of comprehensive kind may be the most
valuable way of monitoring of the headache, dizziness,
concentration, myalgic pains, memory disturbance and
sleep disturbance and specific complications including
seizure disorders, atypical spells and fibromyalgia
that may follow CHITs. The neuropsychiatric evaluation
is not a single interview over forty minutes or an
hour. It cannot be done in one interview: it is too
complex and, moreover, the time based evaluation allows
a film strip view in which the whole system, all the
biopsychofamiliosociocultural elements, must be taken
into account. (Neppe and Goodwin, In Press)

The sequence of such a basic exam involves
outside sources of history and information, demographics
analysis, a detailed main complaint with injury information,
relevant past psychiatric and neurologic history including
any other injuries and any links with lawsuits, a
detailed pharmacologic history including doses, duration,
combinations, responsiveness, side-effects, a history
of abuse of recreational drugs, basic habits, a detailed
computerized history of social and medical facets,
psychological and personality evaluations, obtaining
of collateral information, and detailed neurologic,
psychiatric, mental status, and neuropsychiatric cerebral
cortical evaluations. Furthermore, specialized testing
is then done. All this information is then elaborated
and examined producing diagnoses using a multiaxial
framework of both neurologic and psychiatric kind.
Consequently, management of the patient with a CHIT
requires comprehensive time based evaluations and
significant planning. Such handling is both pharmacological
and non-pharmacological. (Neppe and Goodwin, In Press)

While we have always had pharmacologic
agents that had behavioral effects on brain injured
patients, it was only with the investigations associated
with modern pharmacology that we began to understand
the neurotransmitter systems affected by these agents
and particularly began to notice that some of these
neurotransmitter systems appeared to be disturbed
in various mental illnesses. These studies into the
pathophysiology of head injury have extended, inter
alia, to electrophysiologic measures of sleep, evoked
potentials, reaction times, and ambulatory electroencephalography
. They have further This chapter is not intended to
be complete. It simply highlights several areas of
management in the CHIT patient with the awareness
that management involves two components : further
investigations as necessary and pharmacologic and
other therapeutic interventions.

INTRODUCTION

Four levels of management exist in
the CHIT patient, namely further investigations, cognitive
rehabilitation, non-pharmacologic approaches and pharmacologic
interventions. This chapter focuses on the last -
the pharmacologic - but all four areas are critical.

FURTHER INVESTIGATIONS

After the longitudinal time-based
initial evaluation, additional tests are based on
the specific evaluation. Early on such tests as MRI,
CT and routine sleep and wake electroencephalography
plus supporting blood tests should be performed as
indicated in the previous section (Neppe and Goodwin,
in press). Changes in behavior should be carefully
monitored as accurate diagnosis and evaluation is
a key to appropriate management and further tests
done as indicated.

COGNITIVE REHABILITATION OF THE CHIT PATIENT

Cognitive rehabilitation is exceedingly
important. The potential use of computers in this
regard is an area in its infancy that will rapidly
grow over the next decade. This is also not specifically
focussed on in this chapter.

NON-PHARMACOLOGIC APPROACHES: Basic guidelines
and habits

The following guidelines have been prepared for the
CHIT patient.

1. DIETARY RECOMMENDATIONS
Three regular meals per day are essential Vegetables
and fruit are particularly useful. Avoid highly refined
sugars such as candies Consideration of supplementation
with Vitamins such as E, D, B6 and C or a complex
of multivitamins is warranted. Even Vitamins can be
toxic in high doses so appropriate dosing is important.
Additionally, drug interactions can occur given the
fat solubility of such vitamins as A, E and D. Avoid
saccharins and nutrasweet until it is established
that no specific behavioral effects occur correlating
with these. Significant water intake is useful (hence
the value of water filters) Plenty of exercise regulated
appropriately by the primary care physician is valuable
- graded aerobic elements

2. HABITUAL CONSUMPTION CHANGE:
a. Cut down on any CAFFEINATED beverage consumption.
Because of the presence of symptomatology which may
in part be attributed to the caffeine intake, we recommend
the patient to taper totally off beverages - coffee
tea cola drinks - at the rate of 1 cup per day. Decaffeinated
beverages can be taken as needed instead. Withdrawal
effects such as caffeine withdrawal headache can be
managed with acetaminophen and a slower taper of the
caffeine.

b. Cut down on any ALCOHOL. Besides
direct effects, this will commonly interact with medications
at one or more of four levels: absorption, altered
metabolism, modified responsiveness at receptor levels
and behavioral effects. Unless there are specific
reasons, such as seizures triggered by a tot of wine,
previous or current alcohol or drug difficulties or
such predisposition, aggression or bizarre previous
reactions to alcohol or driving, the occasional small
amount of low potency alcohol (e.g. beer) or medium
potency (e.g. wine) is acceptable.

c. Clearly the use of any PLEASURE DRUGS
of abuse should be avoided.

d. Cut down on SMOKING. This can also
be done using a slow taper. The availability of either
Nicorette gum or Habitrol is a useful usable adjunct
in this regard. Smoking withdrawal is commonly associated
with weight gain and I have recommended that noncalorific
fluids such as water be used instead; appropriate
solids would be lentils, carrots and tomatoes which
can be eaten instead. Moreover, changes in cigarette
habit may result in different prescription needs because
drug interactions or hepatic metabolism may change.

3. PROPER HYGIENE:
a. ALLERGY: An air filter in home may be useful particularly
in the context of any allergy history.

b. BED AND SLEEP: The mattress should
be good and firm; it should be turned regularly; The
pillow should be comfortable; a neck pillow should
be used in the event of neck pain. Any snoring should
be taken seriously and this associated with any other
features of possible sleep apnea, such as day time
fatigue or periods of not breathing noted by others
handled. The value of adequate temperature in the
room - neither hot nor cold cannot be over-estimated.
During winter, if greater fatigue or seasonal variations
of mood arise, the use of a simple timer switch to
create artificial light may be valuable; failing this
more appropriate light therapy may be used, if necessary
and severe enough.

c. NECK A nodule vibrator or equivalent
for the neck in the event of any neck pain may be
useful.

4. SPECIAL ISSUES:
a. MEMORY: Most so-called memory deficits have a significant
functional component frequently relating to the non-specific
symptoms of poor concentration. Valuable is the habit
of recording information in a note-book to be carried
around everywhere. This should include a list of To
Do items and an address book. A cheap watch with multiple
alarms is useful to ensure compliance with medications
and relevant arrangements

b. SPEECH: The use of computerized software
(such as the program Word Foundry by Nordic software)
may be useful for receptive or executive level mild
aphasia. If the initial evaluation is suggestive of
speech pathology, subtle elements could have been
missed such as specific reading disability and an
educational evaluation should be performed.

c. PSYCHOLOGICAL: Express anger by using
a punch bag. Exercise may be useful Loneliness may
be alleviated by joining a social club. Write notes
to self to express distress

d. DRIVING: The operation of any motor
or any other vehicle is always controversial. Most
medications sedate somewhat and even those that do
not may cause paradoxic reactions. On the other hand,
certain conditions such as anxiety, day-time sleepiness,
seizures, poor concentration or memory disturbance
aggravate driving risk and the treatment may be assisting
these problems. Extreme care should be used when driving,
and even when it is deemed safe to drive short distances
in familiar areas, it may be unsafe on longer or unfamiliar
drives. Driving should be avoided in the event of
doubt as to safety to drive not only on behalf of
the patient but the family. Driving a car is always
the ultimate responsibility of the individual driving
it. The physician can advise in cases of uncertainty
- frequently, medication control is safer than the
untreated underlying condition, but any sedation or
slowed reaction times or impaired consciousness or
sleep, visual or memory impairment is a good reason
not to drive.

e. PSYCHOTHERAPEUTIC SUPPORT Supportive
psychotherapy with an appropriately trained therapist
is useful. This should be directed at support with
regard to current problems as well as allowing the
patient a smoother transition as readjustments back
to a healthy core occurs. Depth therapeutic probing,
uncovering many layers of the patients psyche should
be approached only with extreme caution as this may
lead to further decompensation.

f. BEHAVIORAL ELEMENTS: Access to a
firearm, in the context of significant psychopathology
linked with the CHIT, is dangerous. This should be
avoided if at all possible.

g. FOLLOW UP The patient should always
have a regular follow-up primary care physician to
handle any acute problems.

PHARMACOLOGIC INTERVENTIONS

OVERVIEW

Pharmacologic interventions are dependent
on diagnostic evaluation. The four major intervention
groups are:

The azapirone, buspirone, technically an anxioselective
agent, is the most versatile and possibly the
safest of all medications in the CHIT. However,
because of the organicity, even buspirone is sometimes
associated with paradoxic reactions, such as irritability
instead of anti-aggressive effects.

The use of anticonvulsant medication for focal
residual CHITs is critical at times.

Assistance with disruption of the biological
cycle of sleep.

Antidepressant medication is commonly used
to manage the depression and also the pain syndromes.

More uncommon interventions are linked with:

Beta-adrenergic blocking agents like nadolol
and propranolol which are sometimes useful in
situations of autonomic instability with significant
somatization.

Occasional psychostimulant medication is used
for the apathy or for an attention deficit disorder
like condition or for profound sleepiness.

Use of antipsychotic medication such as perphenazine.

Supplements such as minerals , vitamins and
the various fatty acids are all speculative approaches
generally characterized by the absence of specific
medical prescription.

Finally, Analgesics and muscle relaxants may be necessary
to treat pain syndromes. This is not specifically
dealt with below.

Highlights of use of these various medications
and the conditions in which they should be considered
are outlined below with emphasis on specific practical
clinical approaches and needs.

PHARMACOLOGIC PRELIMINARIES:

One should take only the medication
that is needed, the patient should be informed about
the prescription medications and compliance with treatment
is essential.

A. TAPERING OF UNNECESSARY MEDICATIONS
Prior to medicating with extras, one approach is often
to establish that a drug is indeed doing more good
than harm. Tapering or cessation of any medication
prescribed in a CHIT is a reasonable approach when
side-effects are significant or there is a lack of
therapeutic effects

B. SPECIFIC SCHEDULES ON MEDICATIONS
Whenever prescribed, the patient should ensure that
the pharmacist dispensing the prescription give a
package insert which can be read to ensure familiarity
with side-effects. However, this should be in the
context of appropriate medical education by the prescribing
physician and the pharmacist lest the patient distort
side-effects and therapeutic indication which in the
CHIT context is frequently outside labeling. It is
good practice for physicians to develop specific schedules
in this regard prioritizing relevant side-effects
and dosing difficulties. Frequently, side-effects
pertaining to weight gain on such medications as valproate,
tricyclic antidepressants and neuroleptics are not
listed in such inserts. Some effects listed are very
uncommon or may not necessarily be associated with
the medication specifically but may have been coincidental.
The patient should feel free to further discuss these
with the physician.

C. COMPLIANCE
Compliance with medication and cognitive rehabilitation
is critical. Because of memory impairments and amotivation,
it is often necessary to assist with compliance in
the CHIT patient. Medication compliance may be increased
by:

buying a cheap alarm watch with if necessary
multiple alarms.

Mediset or tablet dispensers and medication
being prepared once per week in these dispenser
medisets.

One regular pattern is to take medication at
specific times linked with actions. Patterns of
regularity which is individually determined such
as breakfast, lunch and dinner are useful.

Take medication with water and avoid chocolate
milk or cola drinks or beverages for about half
and hour before and after. Alterations in absorption
pattern may otherwise result.

If taking nonprescribed tablets such as minerals
or vitamins or health store medications then preferably
take them at a different time so that absorption
interactions will be diminished.

Consistency is important.

If a dose is missed, in general, take that
dose as soon as the error is discovered - this
may mean taking one double dose. If several doses
have been missed, take one double dose with the
next dose, then with the following dose a dose
and a half, then regular prescription.

MEDICATION PRESCRIPTION:
Unless specifically indicated, medications are generally
not necessary in a CHIT. However, even if they may
not be necessary at one point, these ideas may serve
as a guide for future management of individual patients.
Treatment is commonly based on symptom alleviation
although chemical regulation with buspirone or putting
out fires with anticonvulsants is sometimes based
on treating the underlying cause.

The four major groups of treatment
(neuromodulation, anticonvulsants, sleep disruption,
antidepressants) and the specific conditions linked
with these medications

1. NEUROMODULATION OPTIONS
Post traumatic head injury characterologic changes
and Personality Disorders and Anxiety Disorders
Following transient traumatic head injury, a range
of central nervous system dysfunctions may ultimately
influence the behavior we site as characterological
disturbances. Organic links (from diverse etiologies)
have been noted particularly in antisocial personality
by Lewis and Bella (1976), Robins (1966), Thomas
and Chess (1977l, and Tucker and Pincus (1980).
Usually these correlate with antisocial behavior
and delinquency that relates to EEG abnormalities,
delayed reaction times, and seizure disorders. (Tucker,
Neppe 1988) The heterogeneous and poorly validated
condition of borderline personality disorder with
fluctuations in affect, intensity of experience,
irritability, frequent suicidal behaviors, aberrant
behavior spells, and brief psychotic features with
total recovery all suggest some temporolimbic instability.
(Tucker, Neppe 1988, 1994); (Tucker et al 1986)

Anxiety is a ubiquitous psychiatric
symptom. Episodes of anxiety, particularly so-called
"panic attacks" may correlate in our experience
with complex partial seizures. Such events were
recognized by Hughlings Jackson last century. (Neppe,
1984A) Most anxieties with head injuries are likely
to be on the psychological side not due to brain
injury however.

BUSPIRONE (BUSPAR) medication. This
is a prime drug for the patient with a CHIT because
of its versatility and safety. The buspirone can
be used for the approved usage of relieving anxiety
/ mixed anxiety depression in the post-traumatic
CHIT. In this instance, the post-synaptic serotonin
1A partial agonist effect comes into play. The usual
dose for anxiety is 10 mg t.i.d., for mixed-anxiety
depression is 15 mg t.i.d. (Neppe, 1990 A, 1989A,
1993A) However, it should alleviate the following
symptoms
sometimes linked with anxiety which are frequently
relate to post-concussional phenomena of the CHIT:
concentration disturbance and also the spectrum
of agitation, irritability, frustration, anger,
aggression (where no FDA approved drugs exist):
Two dose levels of dosage are useful - low e.g.
5 mg t.i.d. which probably reflects autoreceptor
raphe serotonergic nuclei effects; and high for
considerable agitation and co-existing other symptoms
e.g. 20 mg t.i.d. probably reflecting a predominantly
serotonin 1A weak agonist effect. The low dose is
based on the uncontrolled work of Neppe on non-organic
patients and Ratey on mental retardates, the higher
dose on Neppe's research. In many patients, we suggest
initiating dosage at 5 mg t.i.d. built up gradually
by increasing by 5 mg every 3 days to a initial
aim level of 60 mg per day: if the patient develops
non-vertiginous dizziness then drop the dose by
5 mg per day and continue the taper of dose until
no dizziness occurs. Additionally, many CHIT patients
reveal a predisposition towards obsessionality .
Doses of e.g. 20mg t.i.d. probably reflect a predominantly
serotonin 1A weak agonist effect and could be useful
here - the only approved drugs for obsessive compulsive
disorder - Clomipramine (Anafranil) and SSRI drugs
like fluoxetine (Prozac) often have significant
side-effects in this population. Important relevant
side-effects are:

nonvertiginous dizziness - if this occurs
the patient could cut down the dose by 5 mg
per day, the patient should contact the treating
physician and continue the dose at this lower
level without continuing to build up the dose
at that time.

nausea - this suggests that the medication
should be taken with mealtimes - breakfast,
lunch and dinner.

headache and restlessness.

the occasional paradoxic accentuation of
anger or confusion in the organic CHIT patient
- usually an indication that anticonvulsant
is necessary.

2. ANTICONVULSANT OPTIONS Seizure
Disorders
A person is only epileptic when he has seizures
recurrently. An epileptic seizure involves paroxysmal
cerebral neuronal firing which may or may not produce
disturbed consciousness and / or other perceptual
or motor alterations (Neppe, 1988A, B). The most
classical and common epileptic seizures are of the
"grand mal" or generalized "tonic - clonic" kind.
These usually involve relatively short (10-30 seconds)
tonic movements with marked extension / flexion
of muscles but no shaking and then a longer (15-60
sec) clonic tonic manifesting as rhythmic muscle
group shaking. These movements may be associated
with a phase of laryngeal stridor due to tonic muscles
manifesting as a high pitched scream sound. Urinary
and occasionally fecal incontinence may occur due
to sphincteric change and the seizures are almost
invariably followed by headache, sleepiness and
/ or confusion. When preceded by perceptual, autonomic,
affective or cognitive alterations such seizures
are secondarily generalized, as opposed to no original
locus of firing producing focal features prior to
the tonic clonic movements (generalized from the
start) (Neppe, 1982 A ). The different epileptic
seizures are classified in Table 1.

Seizures or other paroxysmal neurobehavioral
disturbances which may not qualify as seizures because
the actual phenomena are not proven to be seizures
are not insignificant post-traumatically. Until
all variants are measured it would be difficult
to estimate exact incidence. This is particularly
so in the context of transient closed head injury.
(CHIT) There is a dichotomy of the possibly 90%
of epileptics who constitute the epilepsy standard
patient who have no more psychopathology than the
average patient and the epilepsy plus patient -
a minority of epilepsy patients having behavioral
or psychiatric abnormalities (Neppe, Tucker 1992).
Seizure disorders present with a high incidence
of behavioral disturbance, which may initially be
interpreted as psychiatric in origin (Neppe, Tucker,
1989, 1994). Many of these relate to the temporal
lobe of the brain. The features of temporal lobe
epilepsy are so varied and so protean that it is
necessary to classify them. Neppe has suggested
the term "possible temporal lobe symptoms" (PTLSs)
for this (Neppe, 1983 A). These are features which
can be induced by stimulating areas of the temporal
lobe during neurosurgery. These symptoms only become
specific symptoms of temporal lobe dysfunction if
their occurrence is validated empirically during
a seizure - either through observation or by the
electroencephalogram (hence the word "possible"
in possible temporal lobe seizures) ( Table 2 )
(Neppe, 1983 B). Using a phenomenological analysis,
Neppe was able to demonstrate that the symptom of
deja vu commonly regarded as symptomatic of temporal
lobe epilepsy indeed had a very special phenomenologic
quality in patients with temporal lobe epilepsy
(Neppe, 1983 A, 1983C ). This involves its association
with post-ictal features such as sleepiness, headache
and clouded consciousness and its link in time with
these features. This association provides an excellent
clue to the existence of temporal lobe epilepsy.
Deja vu is a normal phenomenon occurring in 70 percent
of the population and unless such phenomenological
detail is obtained, patients' symptomatology may
be misinterpreted. Neppe has similarly done such
a study with olfactory hallucinations (Neppe, 1983
B, D, 1982 B). A specific type of temporal lobe
epilepsy olfactory hallucination could not be demonstrated
although there were suggestive features (Neppe,
1984B). A major message, therefore, may be the relevance
of adequately assessing the symptomatology of patients
presenting with epilepsy. It may be that this is
a direction as relevant as electroencephalographic
monitoring (Neppe, 1993 B).

Theoretical biases: Kindling and
Chindling
Kindling may be relevant in head injury. Generally
several events would be required to trigger such
a phenomenon but CHIT theoretically may the straw
that broke the camel's back. We discuss kindling
briefly below.

Kindling involves the progression
of increasingly severe seizure manifestations in
response to electrical stimuli of various areas
of the brain such as the hippocampus, amygdala,
pyriform cortex, or basal ganglia. Such stimulation
is initially sub-threshold, but becomes threshold
when administered repetitively. These sub-threshold
changes, which have been demonstrated in numerous
animal species, at times manifest with behavioral
changes sometimes preceding the motor seizures (Neppe,
1985A,B,C). Neppe recognized that there are distinct
biochemical and other differences between so-called
electrical kindling and the chemical induction of
the process and so developed the term chindling
for the chemical induction of increasingly severe
seizure manifestations in response to general chemical
stimuli (Neppe, 1989 B).

Kindling is increasingly difficult
to induce with the added degrees of encephalization
in primates. If, indeed, the kindling phenomenon
occurs in man, it would probably take many years.
There is indirect evidence for its occurrence in
the development of mirror foci, generalization of
seizures, the alcohol withdrawal paradigm, and possibly
paradigms of response pertaining to nonresponsive
psychosis (Tucker, Neppe, 1988, 1991). However,
kindling has become a very useful theoretical concept
to rationalize interventions pertaining to adjunctive
drugs, particularly anticonvulsants. Whether or
not kindling is shown to be an artifact or not is
probably not of vital importance, for its role may
be as a stimulant to further research.

ANTICONVULSANT PRESCRIPTION
The preferential anticonvulsants in this instance
are not necessarily for a seizure indication, per
se. The subpopulation of CHIT being treated is the
focal residual group. They may manifest with frank
post-traumatic seizures, however, they may have
atypical spells manifesting as the various kinds
of episodic events that we have called paroxysmal
neurobehavioral disorder (PND). Diagnosis is based
clinically, on EEG and on anticonvulsant responsiveness.

The management of epileptics presenting
with behavior disturbance is closely linked to the
discussion of epilepsy in relation to psychopathology.
The heterogeneity of such conditions implies a heterogeneity
of management which is patient based and individually
tailored (Neppe, 1988).

The most important single principle
is anticonvulsant monotherapy. It has been well
demonstrated that the degree of seizure control
is not increased by increasing the number of anticonvulsant
medications. (Neppe, Tucker 1988 A, B) It is more
important to achieve adequate anticonvulsant dosage
and therapeutic ranges on blood levels are often
helpful indicators. However, the object should be
to adequately control all the patient's seizures
and the choice of anticonvulsant is equally important.
Management of patients with seizure disorders involves
primarily appropriate use of anticonvulsants (Neppe,
Tucker, 1988B). In addition, counseling and the
various aspects of psychosocial support, allowing
the patient to live as normal a life as possible,
and to be supported within the framework of the
environment, is also important.

a. CARBAMAZEPINE (Tegretol) is the
primary drug in this group for the CHIT indication
as it seems to have a specific psychotropic effect.
We use it predominantly in the context of temporal
lobe phenomena. It should not to be generically
substituted (Neppe et al, 1988C ). The carbamazepine
in this instance can be used for the approved usage
of relieving seizure disorders or any incidental
neuralgia and sometimes fibromyalgia (unapproved
and unproven). In seizures, the anticonvulsant effect
comes into play. The usual dose for seizures are
200-400 mg t.i.d. or q.i.d. based on monitoring
serum levels to 8-12 ug/ 100 ml and clinical responsiveness
and we have found usually slightly lower doses to
be adequate in atypical spells, PND and temporal
lobe dysfunction e.g. 200 mg tid.

Carbamazepine should alleviate the
following symptoms which are not FDA approved (and
no FDA approved drugs exist): agitation, irritability,
frustration, anger, aggression, mood lability, temporal
lobe symptomatology: The dose levels are probably
in the low therapeutic anticonvulsant range e.g.
6-9 ug/ 100 ml and frequently correspond with an
initial target dose of 200 mg t.i.d. The low dose
is based on the double blind controlled work of
Neppe on patients with EEG temporal lobe abnormalities
and refractory psychosis with hostility and a follow-up
retrospective chart review on hostile atypical psychotics
(Neppe and Bowman, 1991) in which the EEG was normal.
The mechanism may be via kindling or chindling and
episodic phenomena respond best (Neppe, 1990 B).

Generally, a starting dose of 100
mg bid build up by 100 mg every three days to an
initial target dose of 200 mg t.i.d. Important side-effects
relevant for the patient include:

Signs of neurotoxicity : Dizziness, sedation,
diplopia and nausea. Each of these symptoms
may reflect toxicity so that consideration can
be given to one dose being held and the dose
dropped by 100 mg per day pending a blood level
if necessary.

Allergy: Usually a rash - possibly in as
many as one in eight patients - occurs; far
less commonly and more seriously a sore throat,
fever or mouth ulceration may happen: The patient
should stop the medication pending discussion
with the treating physician to establish if
the reaction is drug related.

Extremely rare is the occurrence of bone-marrow
depression which is an idiosyncratic reaction.
There appears to be no correlation of the frequent
and expected drop in white cell count with this
or other immunologic infection predisposition.

Tegretol induces enzymes and may impair control
of conception by oral contraceptives. The usual
practice has been to increase the OC dose slightly
if not contra-indicated for any reason but safer
is to add a second contraceptive method as well.

Prior to beginning the carbamazepine treatment,
the following baseline blood tests should be performed:
Complete blood count including differential cell
count with optional platelet and reticulocyte count.
Hepatic enzymes including Gamma Glutamyl Transferase.
Electrolytes. At subsequent visits, the carbamazepine
levels can be measured and after establishing a
new baseline the CBC and GGT can be monitored as
necessary. Folate, a B vitamin, supplementation
is often necessary based on possible subclinical
deficiency induced by carbamazepine which induces
hepatic enzymes - folate is a co-enzyme in this
cycle. Doses of 5 mg daily are recommended. Calcium
supplementation e.g. as gluconate is also relevant
sometimes. One mechanism may be carbamazepine enzyme
induction producing subclinical Vitamin D deficiency
particularly in a cloudy climate.

b. Other anticonvulsant options are
briefly outlined below:

b. 1. PHENYTOIN (DILANTIN) Adequate
control of seizures with only occasional episodes
suggesting maintaining this drug. However, high
therapeutic levels e.g. 20 ug/ ml are associated
with significantly more cognitive side-effects than
lower levels. Rigidity, slowed thinking, irritability,
sedation, poor psychomotor control and responsiveness
are examples. Consequently, lower doses may be more
logical even with adjunctive second anticonvulsant,
if necessary. Folate and Vitamin D and Calcium supplementation
should be considered. The initial aim dosage is
300 mg daily , as a TID or QD dosing. Phenytoin
can be given intravenously if necessary. Important
side-effects relevant for the patient include:

The change to zero order pharmacokinetics
with potential toxicity with slight dose alterations
or other drugs added.

The gum hyperplasia is a somewhat disabling
long-term effect that is extremely common.

b.2. DIVALPROEX SODIUM (DEPAKOTE). Initiation of
DIVALPROEX SODIUM (also called Valproate) (DEPAKOTE
- not a generic) may be useful particularly with
residual focal frontal lobe phenomena. The Valproate
has an approved usage of relieving seizure disorders
and for prophylaxis of bipolar illness and for headache
prophylaxis. However, it could alleviate the following
symptoms which are not FDA approved: agitation,
irritability, frustration, anger, aggression, mood
lability, temporal lobe symptomatology (no FDA approved
drugs exist) but there is limited clinical use in
these areas because frequently there is limited
effectiveness. A starting dose of 250 mg t.i.d.
is suggested. The usual dose for seizures are 250-1000
mg t.i.d. or q.i.d. based on clinical responsiveness
mainly but also -far less reliable with valproate
- monitoring of serum levels to 70-100 ug/ 100 ml.
For non-approved uses slightly lower doses e.g.
250 mg-500 mg t.i.d. or q.i.d. with similar blood
levels to seizures may be appropriate. Whether the
mechanism then is anticonvulsant or psychotropic
is unknown.

A major advantage of valproate is
it is generally well tolerated with few side-effects
and less sedative than carbamazepine. Important
side-effects relevant for the patient include:

Nausea is common: give with meals.

Dizziness, sedation and diplopia but these
are uncommon. Each of these symptoms may reflect
toxicity so that consideration can be given
to one dose being held and the dose dropped
by 250 mg per day pending a blood level if necessary.
Supplemental carnitine has been suggested both
to prevent hepatotoxicity and diminish any cognitive
side-effects. Dosing is disputed but 500 mg
qd may be reasonable.

Allergy is rare.

Extremely rare is the occurrence of hepatotoxicity.
There appears to be a correlation with anticonvulsant
polytherapy in infants and in adults the drug
should be safe.

Most psychotropics will push up the Valproate
level and it will do likewise. Carbamazepine
may lower it. Valproate does not induce enzymes.

Many patients complain of weight gain which
may be the most significant common side-effect
and reason for discontinuation.

Prior to beginning the Valproate treatment, the
following baseline blood tests should be performed:

At subsequent visits, the valproate levels
can be measured and after establishing a new
baseline the CBC and GGT can be monitored as
necessary.

b. 3. GABAPENTIN (NEURONTIN) This new anticonvulsant
has the advantage of low toxicity, low range of
side-effects and no known drug interactions. Serum
levels are not helpful for clinical practice as
they are non-correlative with therapeutic range
or toxicity and they are, in general, unavailable.
Technically gabapentin is an adjunctive anticonvulsant,
but it may be tried in monotherapy for specific
symptoms. Doses of 100 mg t.i.d. are low average
although 20% get sedated so start low 100 mg daily
building by 100 mg QOD till better control e.g.
300 mg t.i.d.

b.4. LAMOTRIGINE (LAMICTAL) This new
anticonvulsant in the United States had been marketed
in numerous countries before that. It has remarkable
effects on some although in our experience patients
may initially become paradoxically worse with each
increase in dose. Like gabapentin, serum levels
are unnecessary and unavailable. Technically, it
too is an adjunctive anticonvulsant, but it may
be tried in monotherapy for specific symptoms. Doses
of 25 mg daily built up to 100-200 mg bid over several
weeks are average.

b.5. TOPIRAMATE (TOPIMAX) and TIAGABINE
(GABATRIL) These are new anticonvulsants in the
United States Tiagabine marketed October 1997).
Topiramate comes in 25 mg, 100 mg and 200 mg sizes.
Begin with 25 mg bid and build if necessary to up
to 400 mg daily. Tiagabine has small milligram sizes
with the starting dosage of about 4 mg daily and
the usual dosage of 12 through 40 mg per day. Both
drugs are useful as adjunctive therapy in patients
whose seizures are uncontrolled on monotherapy particularly
in partial seizures. Side-effects for both are rather
typical for anticonvulsants namely fatigue and psychomotor
impairments.

3. THE BIOLOGICAL SLEEP CYCLE DISRUPTION:
Sleep disorders
One of the most common complaints after CHIT is
sleep disturbance which may take months or years
to fully improve. Many such complaints may be psychiatrically
linked, however, some may have biological bases,
linked with the conditions above. Sleep disorders
are among the most fundamental of all psychiatric
disorders, and certain psychiatric illnesses may
well have a very profound base with regard to sleep
disturbance. For example, a diagnosis of mania may
be nearly impossible without a profound decrease
in total sleep time and, in fact, most manics have
a period of at least 36 hours where they do not
sleep at all and during which they do not feel fatigued
(Tucker, Neppe, 1988) Similarly, a shift with phase
advance and a decreased latency to rapid eye movement
sleep is characteristic of a biological depression.
Another common symptom in this condition is terminal
insomnia - early morning waking. This may or may
not be correlated with this phase advancement as
the two have not been investigated (Tucker, Neppe,
1988).

Sleep disturbance is of profound importance
in the CHIT but may reflect underlying affective
disorder or personality. Many patients with profound
degrees of antisocial personality give a history
of sleep disturbance involving paroxysmal wakenings
since childhood. Many brain impaired individuals
may have periods during which they nap during the
day.

HYPNOTICS: When sleep is impaired
significantly hypnotics may be considered. Options
include zolpidem (FDA approved), trazodone (approved
as antidepressant but commonly used) and melatonin
(non-prescription hormone)

a. ZOLPIDEM TARTRATE (AMBIEN) medication.
This is a imidazopyridine nonbenzodiazepine hypnotic
with no apparent dependence, and normalization of
sleep cycles with extensive European experience
(5 mg pink or 10 mg white tabs - breakable). It
acts at the omega 1 sites of GABA - a receptor preferentially.
It is FDA indicated for short-term management of
insomnia. It has rapid onset, and short half life
(2-3 hours).

b. TRAZODONE (DESYREL) medication.
Trazodone is marketed as an antidepressant: it does
not have anticholinergic side-effects and has little
cardiotoxicity. In sub-antidepressant doses such
as 50-100 mg, it is frequently used as a hypnotic
because it is sedative with little carry-over to
the next day and has excellent physiological effects
on slow wave sleep. Patients should be warned that
it may drop blood pressure and induce tachycardia
- hence they should go to bed after taking it until
they know what effects it has on them. In males
there is a rare side-effect of priapism (1 in 8000
males) which can usually effectively be treated
with pseudo-ephedrine hydrochloride and immediately
packing the penis with ice.

c. MELATONIN: Given the biological
sleep disturbance component and disturbances in
diurnal rhythms, Melatonin is a non-prescribed option
left to the patient's choice. The following key
information should be communicated:

the lack of research on the drug

questions on purity of the preparations which
could lead to unusual reactions (other health
food store preparations could have the same
problem).

interactions with other drugs

possible long-term suppression of the pineal
(speculative only) based on other neuroendocrine
responses to, for example, thyroxin and steroid
in thyroid and adrenal suppression, which implies
tapering of the melatonin in the event of stopping.

other unknown effects, pharmacokinetic and
pharmacodynamic.

On the other hand, melatonin remodulation appears
physiological. This has not been prescribed per
se but is available in certain health food stores
in a 3 mg and 5 mg size. Preferable is the smallest
possible dose as physiologically it is thought only
0.5 mg - 1 mg is necessary in the normal person.
Preparations of animal extraction should be avoided
at this point: vegetable or synthetic melatonin
may prove less risky. The drug is best taken an
hour before dusk and should take several weeks to
work fully.

d. Benzodiazepines: Benzodiazepines
should be avoided, if possible, because of their
addictive qualities and impairments at the psychomotor,
cognitive, amnesic and drug interactional levels.
The benzodiazepine may relieve symptoms non-specifically
and incompletely but has all the cognitive, psychomotor,
and dependence, addictive problems of this drug
group. This may be aggravated by previous abuse
history and symptomatic status.

e. Sleep disturbance usually appears
secondary in the CHIT and should be managed with
no napping during the day.

4. MANAGEMENT OF DEPRESSION AND MOOD
DISORDER: Affective Disorders and Head injury
The area of mood disorders allows possible practical
and theoretical understanding of the role of the
central nervous system in behavior disorders. Affective
disturbances may be triggered or induced by head
injury with or without patients with traumatic temporal
lobe epilepsy (Neppe, Tucker 1994) and head trauma
(Neppe, Tucker 1994; Tucker, Neppe 1991).

We believe that CHIT may trigger "Depressive
pseudodementia" in patients with limited cerebral
reserve (MacAllister, 1983, 1992). This refers to
the organic symptomatology, particularly dementing
symptoms in affectively disturbed patients. Cognitive
and neuropsychologic disturbances are associated
with affective disturbances generally reversible
with treatment. Consequently, in dealing with the
demented patient, one must rule out affective disturbance
in the older patient (Neppe, Tucker 1994).

a. LITHIUM CARBONATE (ESKALITH AND
OTHERS - choice is optional): occasionally lithium
is useful when patients manifest cyclical phenomena
of their residual focal CHIT. Medication problems
with lithium are linked commonly to tremor which
is a rather coarse static one which patients find
impairing in functionality and embarrassing. Some
patients become nauseous and/ or confused. Our preference
is to lower dosage in the event of any of the above
symptoms. Baseline blood tests of electrolytes and
renal functions are important as is frequent monitoring
for a major but neglected long-term complication
nephrogenic diabetes insipidus commonly presenting
as polyuria or nocturia. One way to initiate lithium
is by giving 600 mg on the first day and check a
level after 24 hours. This will also screen for
those who become Lithium toxic rather quickly. Lithium
is an extremely lethal compound and should be used
under supervision of a psychiatrist. Two different
blood levels can be considered: Low dose with less
side-effect potential but possibly less control:
aim at a blood level of 0.4-0.6 meq / L. High dose
with more side-effect potential but possibly more
control: aim at a blood level of 0.7-0.9 meq / L.
Many colleagues use higher doses but this would
not be my preference in this instance.

b. ANTIDEPRESSANT options can be applied
in the context of mobilization of significant or
major depression either post-traumatically or post-concussionally
in the CHIT or in alleviation of pain (not approved).
Our preference is to avoid the SSRIs group as well
as the tricyclics and to use nefazodone or venlafaxine
as selective drugs acting reasonably physiologically
at the norepinephrine and serotonin receptor levels.
Bupropion may also be of value.

b.1. NEFAZODONE (Serzone): This antidepressant
of triazolopyridine structure has ideal theoretical
elements both for agitated and retarded depression.
The reason relates to its modulating SSRI properties
which implies less side-effects such as agitation,
anxiety, sexual related pathology, nausea, akathisia
and suicidality. It has additionally serotonin 2
blocking effects which should enhance both antidepressant
and anti-aggressive properties and further diminish
SSRI side-effects. It is more sedative than the
other SSRIs but far less than the triazolopyridine,
Trazodone. My preference is to start with doses
of 50 mg bid and increase every 3 days by 50 mg
daily, always giving bid dosing until an initial
dose of 200 mg bid is achieved. Doses should best
be given in the morning and afternoon because of
its short half life and uneven kinetics. Costs of
all sizes are equal - 200 mg, 150 mg, 200 mg, 250
mg. Serzone inhibits the 3A4 part of Cytochrome
P450 enzyme system in the liver. This increases
levels of certain chemicals e.g. ketoconazole, alprazolam,
triazolam, and probably SSRIs like fluoxetine as
well as some calcium channel blockers. These substances
should increase Nefazodone levels as well and a
50% dose adjustment is general rule. Particularly,
do not give with Seldane (terfenadine) and Hismanal
(astemizole) - if necessary change to Claritin (Loratadine)
(10 mg Claritin usually equal to 10 mg Hismanal,
60 mg bid of Seldane)

b.2. Venlafaxine (Effexor) This has
the advantage of acting at both serotonin ("sledgehammer"
pharmacologic) and norepinephrine ("chisel" and
more physiologic) and should not produce the sexual
dysfunction of the SSRIs. Its limitations relate
to possible nausea, escalated blood pressure and
agitation. It is logical in the retarded depressive
patient.

b.3. Bupropion (Wellbutrin): This
antidepressant likely acts clinically through a
somewhat irreversible norepinephric re-uptake inhibitor
effect of an active metabolite hydroxy bupropion
and not the dopaminergic effect previously thought.
Bupropion differs from most antidepressants in its
absence of effect on serotonin. Given the availability
of a long-acting form, twice daily dosing is logical
with a starting dose of 75 mg twice per day building
if necessary to 300 mg daily. Likely choice is based
on amotivation, the norepinephric effect supplementing
serotonergic drugs if necessary, lack of sexual
dysfunction, overweight status, and need for some
activating action.

b.4. In our opinion, the following
antidepressants are not usually recommended in the
CHIT patient with depression, but are commonly prescribed
by some - the tricyclic antidepressant and the selective
serotonin re-uptake inhibitor groups. I. Tricyclic
antidepressants like nortriptyline, imipramine and
desipramine. The tricyclic group has problematic
side-effects namely potential epileptogenicity,
memory impairments, cardiotoxicity due to arrhythmias,
anticholinergic effects such as urinary retention,
dry mouth, blurred vision and constipation, interaction
with alcohol, and sedation. In the CHIT patient,
the dysmnesic and seizure elements are particularly
troublesome.

NORTRIPTYLINE (Aventyl, Pamelor) medication.
This tricyclic antidepressant is potent and can
be used frequently in doses of 75 mg per day in
instances requiring 150 mg of similar other tricyclic
agents. Moreover the monitoring of blood levels
to an antidepressant therapeutic window allows easy
evaluation particularly in the complex patient on
carbamazepine. Its effects are predominantly serotonergic.

IMIPRAMINE (Tofranil) medication for
biological depression is linked with seizures This
is two-edged as it may exacerbate seizure phenomena.
This tricyclic antidepressant is potent and can
be used frequently in doses of 75 mg-150 mg per
day in this case. Its effects are predominantly
adrenergic.

DESIPRAMINE (Norpramin) medication.
This tricyclic antidepressant is not very potent
mg for mg and is used frequently in doses of 150-225
mg per day. It is a breakdown product of imipramine.
In practice, it is more activating, less sedating
and causes more sweating than the more sedative
tricyclics. Its effects are predominantly noradrenergic.

II. Selective Serotonin Re-uptake
Inhibitors (SSRIs) like fluoxetine, paroxetine and
sertraline. This group of drugs do not have the
anticholinergic nor cardiotoxic side-effects of
the tricyclic antidepressants. However, they are
potent serotonergic agonists with no way to diminish
the effect other than breakdown of active compound.
These drugs have two problematic common side-effects
namely nausea and sexual dysfunction. They may paradoxically
increase anxiety, irritability and agitation, accentuate
nausea and disrupt sleep. There is a possible discontinuation
syndrome, and clinically frequently loss of effects,
or need for escalating dosage occurs over time and
it is for these reasons particularly that we do
not recommend the SSRIs to the CHIT patient. The
serotonergic effects of all the current SSRIs appear
non-specific on supposedly all serotonin receptor
subtypes. As such, the risk of paradoxic reactions
is theoretically higher.

FLUOXETINE (Prozac) with its extraordinarily
long half-life (>400 hours including the metabolite
norfluoxetine) should be used with extreme caution.
In fluoxetine particularly there is controversy
surrounding precipitation of suicidality, aggression,
akathisia and tardive dyskinesia.

PAROXETINE (Paxil) does not have an
active metabolite but it inhibits the hepatic P450
cytochrome enzyme system. It has a one day half
life. Start with doses of 20mg per day initially
and later 30 mg per day built up as necessary to
50 mg per day. SERTRALINE (Zoloft) has a minor probably
non-significant active metabolite. We now know that
it does effect the hepatic P450 cytochrome enzyme
system so there may be drug interactions. It has
a slightly longer half life than paroxetine - several
days. Start with doses of 25 mg per day (half of
50 mg tablet) initially for three days and then
50 mg per day built up as necessary to 100 mg per
day.

MORE UNCOMMON PHARMACOLOGIC OPTIONS
FOR THE CHIT PATIENT

1. PHYSIOLOGIC RESTABILIZATION by
BETA-BLOCKADE if numerous somatic - bodily - symptoms
exist may be considered. NADOLOL (CORGARD) medication.
Beta-blockers are useful in this instance for the
somatic features of anxiety and agitation. They
are not specifically FDA approved for these indications.
Nadolol is suggested as the only poorly lipid soluble
broad-spectrum (B1 and B2) beta-adrenergic blocker
which can act peripherally and because of lack of
intrinsic sympathomimetic activity can be dosed
according to pulse. The dose is similar to that
of propranolol (Inderal). The initial starting dose
usually suggested is half 20mg tablet t.i.d. i.e.
10 mg t.i.d. We suggest this be built up gradually
by increasing by 10 mg every 3 days to a initial
aim level of mg per day. The drug should be administered
as a t.i.d. dosage and was chosen over other beta-blockers
because it is not very lipid soluble (avoiding central
side-effects), has both beta1 and 2 effects and
has no intrinsic sympathomimetic activity so that
an initial titration of dose to a pulse of 66/ minute
can be aimed at. Important side-effects relevant
for the patient include:

Precipitation of asthma, diabetes, hypotension,
cardiac failure and peripheral vascular disease
leading to these conditions being contra-indicated.

The awareness that too much is being taken
if the pulse goes into the fifties.

To contact the treating physician if signs
of cardiac failure such as pedal edema develop.

If the response to the nadolol is partial, we suggest
changing to a lipid soluble betablocker - to propranolol
(Inderal) and building up to a dose of about 480
mg per day or till side-effects or till pulse is
= 60/minute. The change around from nadolol can
be mg for mg and direct substitution from 40 mg
t.i.d. nadolol to 40 mg t.i.d. of propranolol. Thereafter
maintain the dose for 1 week and increase by 20mg
t.i.d. more per week till 120 mg qid or pulse =
60/min pre-dosage or side-effects such as dizziness
(Neppe, 1989 C).

2. PSYCHOSTIMULANTS are occasionally
worth considering in the CHIT particularly in the
context of residual focal non-episodic phenomena
and / or a history of paradoxic responses. These
drugs should be used with caution based on potential
dependence, misuse (also by others), tics and possible
tachyphylactic effects. One approach is to use these
drugs in both attention deficit disorder and narcoleptic
syndromes as provocative pharmacologic tests: non-response
without side-effects = increase the dose; worsening
= take patient off; improvement = maintain.

One preference is generally for the
scheduled methylphenidate (Ritalin) which appears
more effective than pemoline (Cylert) (which requires
liver function tests six monthly) but requires bid
or tid dosing; it should also be safer than dextro-amphetamine
sulphate (abuse potential, possible potential to
a "model psychosis" / paranoid syndrome). Start
with 10 mg qd and build up to 10 mg tid initially
over 10 days. The patient should record responsiveness.

A second preference is for pemoline
(Cylert) (which requires liver function tests six
monthly) but is less highly scheduled, less likely
to be abused? and cause tics? and can be given daily
but it may be less effective than methylphenidate
(Ritalin); it should also be safer than dextro-amphetamine
sulphate (abuse potential, possible potential to
a "model psychosis" / paranoid syndrome). Start
with 37.5 mg qd and build up to 75 mg qd initially
over 10 days. The patient should record responsiveness.

3. ANTIPSYCHOTIC USE: Psychotic Disorders
and Head injury
There are many neurologic causes of psychosis (Table
1), particularly seizure disorders and more so complex
partial seizures (or temporal lobe epilepsy). This
may be a possible link of the rare onset of paranoid
psychosis after brief traumatic brain injury. In
1963, Slater and Beard pointed out that all of the
symptoms that have been observed in schizophrenic
patients can occur in patients with seizure disorders.
Recent efforts using standardized diagnostic rating
scales have shown that the positive symptoms of
the psychotic state of patients with temporal lobe
seizure disorders is almost identical to schizophrenics
(Trimble, 1982; Toone, 1981). Seizure disorders
present with a high incidence of behavioral disturbance,
which may initially be interpreted as psychiatric
in origin (Neppe, Tucker, 1994). The range of behavioral
symptoms is listed in Table II and most patients
have only one or two of these symptoms that remain
consistent over the course of the illness. (Neppe,
1989 D)

NEUROLEPTICS (antipsychotics; also
called major tranquilizers) should be avoided in
the head injured as there is a higher risk of tardive
dyskinesia (Neppe, Holden, 1989; Neppe 1989 D).
Exceptions relate to the very occasional presence
of or exacerbation of psychosis. PERPHENAZINE (TRILAFON)
medication has become our preferential drug in post-traumatic
psychosis as part of the residual focal elements
of the CHIT. Perphenazine is approved for use in
psychotic conditions. Amongst the important side-effects
discussed is the long term risk of tardive dyskinesia
and related syndromes and its relevance to diagnosis,
dosage, duration of treatment, smoking epidemiology
and the limited amounts of treatment. Anticholinergic
medication is sometimes prescribed to alleviate
the extra-pyramidal side-effects of neuroleptic
drugs. The patient should not routinely receive
anticholinergic agent with the perphenazine as this
complicates pharmacokinetics, may accentuate psychosis,
is usually unnecessary and disputably increases
the risk of tardive dyskinesia. Additionally, anticholinergics
mask neuroleptic dosage somewhat. Also, additional
potential side-effects of dry mouth, dilated pupils
with blurring of vision, constipation, confusion,
memory impairment and delirium may occur (Neppe,
Ward, 1989). When there is a previous history of
response to anticholinergics but with side-effects
of sedation, an anticholinergic which is relatively
non-sedative, has low abuse potential, and which
moreover has some muscle relaxant effect, orphenadrine
(Norflex) is recommended. Usual doses are 50 mg
TID. If not tolerated, lower doses can be tried.
A maximum of 100 mg tid should be used. The most
commonly used anti-Parkinsonian anticholinergic
in the USA appears to be benztropine (Cogentin).

4. SPECIAL REPLACEMENT OF VITAMINS,
MINERALS AND FATTY ACIDS. This is speculative only:

a. ANTI-OXIDANTS A recent area of
some interest, theoretical speculation and difficulty
appreciating cause-effect relationships and consequent
therapeutic efficacy is the use of anti-oxidant
medications in instances of neuronal or neurologic
diseases including pervasive developmental disorder,
Landau-Kleffner syndrome, atypical epilepsies, multiple
sclerosis, and mental retardation. These organic
brain conditions may or may not prove to have end
point biochemical similarities with CHIT. Anti-oxidants
should be considered if the profile includes abnormal
glutathione enzymes like Glutathione peroxidase
and transferase, and various trace elements like
Selenium plus a Lipid peroxide index. These cannot
be measured but speculatively may be abnormal in
a CHIT with residual or post-concussional elements.
The following guidelines are thought appropriate
at this time:

b. MINERAL, VITAMIN, OMEGA SUPPLEMENTATION
Chromium picolinate 200 ug to 400 ug daily, Magnesium
ion e.g. as chloride 400 mg per day (with some calcium
if necessary to avoid diarrhea), and Zinc 15 mg
daily and the Omega fatty acids are interesting
mineral and vitamin or food supplements in this
kind of patient. There is limited uncontrolled or
anecdotal or lay literature suggesting this combination
may assist potential towards hypoglycemia and may
allow weight control (particularly chromium based
on its controversial effect in relation to glucose
cell utilization and possibly zinc), lower risk
of heart attack (magnesium particularly) and diminished
seizure risk (magnesium and secondarily chromium).
Obviously, such supplementation is unnecessary in
some but as it is not easy to distinguish in any
particular case, and the patient may wish to explore
these possibilities ensuring that the best quality
brands are bought and knowing that besides risks
linked with the vehicles containing these medications
(as with any vitamin or mineral or sometimes generic
type medication) there may be unknown interactions
occurring.

CONCLUSION:

We are doing a full circle. Cesare
Lombroso, last century wrote about the constitutional
psychopath (Lombroso, 1912). Sociologists and behaviorist
psychologists claimed that there were no such constitutional
givens and that all behavior was socially determined
totally ignoring the organism. We have now returned
to the stage where constitutional and biologic components
have again become important and well demonstrated
in our conceptualization of transient traumatic
head injury.